Safety and Efficacy Study of Creatine and Tamoxifen in Volunteers With Amyotrophic Lateral Sclerosis (ALS) (SDALS-001)

• Decline in ALSFRS-R [ Time Frame: 38 weeks of treatment followed by a telephone interview at 42 weeks. ] [ Designated as safety issue: No ]
  Primary efficacy will be assessed by analyzing the mean rate of decline in the ALS Functional Rating Scale-Revised (ALSFRS-R) score over nine months.
  
  

• Vital Capacity/Pulmonary Function Testing [ Time Frame: 38 weeks of treatment followed by a telephone interview at 42 weeks. ] [ Designated as safety issue: No ]
  Secondary efficacy will be assessed by analyzing the change in the Slow Vital Capacity score over nine months.
  
  
• Tracheostomy-free survival [ Time Frame: 38 weeks of treatment followed by a telephone interview at 42 weeks. ] [ Designated as safety issue: No ]
  Secondary efficacy will be assessed by analyzing rate of tracheostomy-free survival at nine months.
  
  
• Incidence of Falls [ Time Frame: 38 weeks of treatment followed by a telephone interview at 42 weeks. ] [ Designated as safety issue: No ]
  Secondary efficacy will be assessed by analyzing the estimated mean rate of falls over nine months.
  
  
• Analysis of Safety and Tolerability Measures [ Time Frame: 38 weeks of treatment followed by a telephone interview at 42 weeks. ] [ Designated as safety issue: Yes ]
  The safety data will be summarized according to treatment arm. Total number of AEs, AEs that cause study drug withdrawal and abnormal laboratory tests will be compared among treatment arms.
  
  

Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disorder that results in progressive wasting and paralysis of voluntary muscles. It is known that nerve cells called motor neurons die in the brains and spinal cords of people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is unknown.

In this double blind, randomized, selection design trial, researchers will evaluate the safety and effectiveness of creatine and tamoxifen in volunteers with ALS. There are a large number of potential drugs that may improve the survival or slow down the disease progression in people with ALS. The current strategy is to test one drug at a time against placebo. "Selection Design" is a different type of study design. A Selection Design study uses multiple drugs to screen against each other and picks the winner to take to a larger study. This design can speed the search for effective drugs to treat ALS. In this Selection Design study, each volunteer will take one active study drug (creatine 30gm, tamoxifen 40mg, or tamoxifen 80mg) and one placebo.

Approximately 60 eligible volunteers with ALS will be recruited from multiple centers in the US that belong to the Northeast ALS Consortium (NEALS). Volunteers will be randomly assigned equally to the three treatment arms: creatine 30gm/day, tamoxifen 40mg/day and tamoxifen 80mg/day. Volunteers will take study treatment for 38 weeks. After screening and randomization, volunteers will be followed at weeks 4, 10, 18, 28 and week 38. A final telephone interview will occur at week 42 (off study drug).